A deep look at KIR–HLA in Amerindians: Comprehensive meta-analysis reveals limited diversity of KIR haplotypes

Augusto, Danillo G.; Hollenbach, Jill A.; Petzl-Erler, María Luiza

doi:10.1016/j.humimm.2015.01.025

Cited by 16 publications

(15 citation statements)

References 62 publications

(36 reference statements)

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“…This allele has been found to be associated with chronicity for both hepatitis B and hepatitis C and is also a susceptibility factor for Ebola virus . Furthermore, it was absent from the majority of KIR haplotypes identified in other Amerinidian tribes studied, which have haplotypes containing KIR2DS5 rather than KIR2DS3 . These data raise the possibility that KIR2DS3 has been selected against in these populations and, coupled with data from infectious disease association studies, suggest that it may confer clinically important susceptibility to viral infections.…”

Section: Kirmentioning

confidence: 72%

NK cells: tuned by peptide?

Das

Khakoo

2015

Immunological Reviews

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Natural killer cells express multiple receptors for major histocompatibility complex (MHC) class I, including the killer cell immunoglobulin-like receptors (KIRs) and the C-type lectin-like CD94:NKG2 receptors. The KIR locus is extremely polymorphic, paralleling the diversity of its classical MHC class I ligands. Similarly, the conservation of the NKG2 family of receptors parallels the conservation of MHC-E, the ligand for CD94:NKG2A/C/E. Binding of both CD94:NKG2 heterodimers and KIR to their respective MHC class I ligand is peptide dependent, and despite the evolution of these receptors, they have retained the property of peptide selectivity. Such peptide selectivity affects these two systems in different ways. HLA-E binding non-inhibitory peptides augment inhibition at CD94:NKG2A, while HLA-C binding non-inhibitory peptides antagonize inhibition at KIR2DL2/3, implying that KIRs are specialized to respond positively to changes in peptide repertoire. Thus, while specific KIRs, such as KIR2DL3, are associated with beneficial outcomes from viral infections, viral peptides augment inhibition at CD94:NKGA. Conversely, NKG2A-positive NK cells sense MHC class I downregulation more efficiently than KIRs. Thus, these two receptor:ligand systems appear to have complementary functions in recognizing changes in MHC class I.

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Section: Kirmentioning

confidence: 72%

NK cells: tuned by peptide?

Das

Khakoo

2015

Immunological Reviews

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“…NKs principally contribute to innate immunity and also adaptive immune responses by killing the targeted cells of theirs and production of a variety of cytokines and chemokines [37]. Overall, upon interaction with their ligands which are usually HLA class I, KIR provide inhibitory or activating signals to regulate the activity of NKs, which contributes to pathogenesis of diverse kinds of diseases [41], [42]. Different compounds of KIR-HLA genotypes can induce different thresholds of activation in NK family and such genotypic variations have been found to be associated with a number of human diseases and complications including viral infections, autoimmune disorders and cancers [43] as well as reproduction abnormalities [44], [45].…”

Section: Resultsmentioning

confidence: 99%

Colorectal cancer and the KIR genes in the human genome: A meta-analysis

et al. 2016

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Colorectal cancer is one of the most common types of inflammation-based cancers and is occurred due to growth and spread of cancer cells in colon and/or rectum. Previously genetic association of cell cycle genes, both proto-oncogenes and the tumor suppressors has been proved. But there were few studies about association of immune related genes such as killer-cell immunoglobulin-like receptors (KIRs). Thus we intend to perform a meta-analysis to find the association of different genes of KIR and susceptibility to be affected by colorectal cancer. The overall population of the four studies investigated in our meta-analysis was 953 individuals (470 individuals with colorectal cancer and 483 individuals in control groups). After the analyses, we concluded that colorectal cancer is affected by KIR2DS5 and also there were no protecting gene. This result shows the inflammatory basis of this cancer. In other words, in contrast to leukemia and blood cancers, colorectal cancers seem to be affected by hyper activity of natural killer-cells (NKs). Whys and therefore of this paradox, is suggested to be investigated further.

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“…Several studies have demonstrated that Native American populations have a differentiated pattern of variability in the immune system, either in HLA-KIR diversity or in the adaptive profile (Tsuneto et al, 2003;Augusto et al, 2013Augusto et al, , 2015Lindenau et al, 2013). They showed a reduced number of HLA and KIR alleles in relation to non-Native populations, that was considered as one of the explanations for their differentiated susceptibility to introduced diseases (Augusto et al, 2013(Augusto et al, , 2015Lindenau et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…There are several evidences showing that Native American populations are immunologically different from non-Native populations (Hurtado et al, 2004;Lindenau et al, 2013). Several investigations reported that Native American populations have a lower variability in several immune system genes such as KM, GM, Kell, HLA, and KIR (Bhatia et al, 1995;Black and Pandey, 1997;Black, 2004;Prugnolle et al, 2005;Augusto et al, 2013Augusto et al, , 2015. Recently it has been reported that the pattern of adaptive immune system variability in Amerindians populations differs from that observed in the HapMap CEU population as evaluated by F ST analyses (Lindenau et al, 2013).…”

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confidence: 99%